Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A bispecific monoclonal antibody, reactive with methotrexate (MTX) and a tumour associated antigen (gp72) has been produced by fusing spleen cells from MTX immunised mice with 791T/36/3 (anti-gp72) hybridoma. The hybrid antibody was purified from anti-MTX and anti-gp72 antibodies present in the hybridoma culture supernatant by combinations of affinity chromatography on a MTX-agarose immunoabsorbent and stepwise acid elution from Sepharose-Protein A. A particular feature of the present antibody is that it reacts with conjugated MTX; this would allow in vivo targeting of conjugates, increasing many fold the number of molecules of drug carried or localising to pre-targeted antibody. Dual binding between tumour cell surface antigen and MTX was demonstrated by the ability of the hybrid antibody to bridge between tumour cells and MTX as MTX-HSA conjugate, reaction here being detected by flow cytofluorimetry. Purified hybrid antibody specifically enhanced the in vitro cytotoxicity of MTX-HSA for gp72 positive tumour cells.
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PMID:A bispecific monoclonal antibody against methotrexate and a human tumour associated antigen augments cytotoxicity of methotrexate-carrier conjugate. 233 36

Desensitization of human basophils with anti-IgE antibody or antigen induced an increased sensitivity to the phorbol ester TPA, evidenced as 2-5 fold increase in the potency of TPA to induce histamine release. As noted in previous publications the magnitude of the change in sensitivity to TPA was a function of the extent of cell surface IgE crosslinking. Thus, the density of cell surface antigen-specific IgE determined the magnitude of the curve shift and the multivalent antigen, BPO21-HSA was found to produce a greater curve shift than the simpler bivalent hapten, BPO2, in accord with previous studies which demonstrated that BPO2 was a "weak" stimulus compared to BPO21-HSA. Basophils which had been fully desensitized by prior treatment with anti-IgE or antigen in the absence of calcium also displayed the curve shift for at least 24 h after desensitization. However, the change induced by crosslinking which altered the cells' sensitivity to TPA required the continued presence of crosslinks and was therefore not the result of a permanent alteration induced by desensitization. Basophils which were fully desensitized to BPO7-HSA demonstrated the curve shift provided that the antigen-induced crosslinks were maintained: treatment with monovalent hapten, BPO-EACA, rapidly returned the cell response to TPA to control, non-desensitized, levels. Since TPA is thought to act by activation of protein kinase C (PKC) we demonstrated that BPO-HSA induced crosslinking increased PKC activity and that the increased activity persisted unless antigen-induced crosslinks were dissociated by the addition of monovalent hapten.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Persistence of early crosslink-dependent signal transduction events in human basophils after desensitization. 245 86

We previously postulated that desensitization of human basophils was due to endocytosis or shedding of IgE and/or its Fc receptor. We report here, however, that during a 3-hr desensitization of purified basophils, there was no loss of cell surface antigen-specific IgE. The specific desensitization induced by antigen persists for at least 24 hr whereas simultaneously occurring nonspecific desensitization can recover during the same time interval. Therefore, we suggested that specific desensitization may result from a permanent modification of the Fc receptor or some closely associated protein. On the basis of elution studies of 125I-labeled BPO-HSA, we also suggest the antigen antibody reaction matures to aggregates of increasing size, and we propose that these large aggregates, unable to initiate a release signal, cause an additional component of desensitization.
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PMID:Studies of antigen binding on human basophils. II. Continued expression of antigen-specific IgE during antigen-induced desensitization. 618 51

Corrective gene transfer for therapeutic intervention in metabolic and hematopoietic disorders has been hampered by the relatively inefficient transduction of human hematopoietic stem cells. To overcome this, a bicistronic recombinant retrovirus has been generated that delivers both a therapeutic glucocerebrosidase (GC) cDNA for the treatment of Gaucher disease, and a small murine cell surface antigen (heat-stable antigen [HSA]) as a selectable marker. An amphotropic retroviral-producing cell clone was created, and filtered supernatant was used to transduce NIH 3T3 cells. Sorting of transduced cells by flow cytometry enabled separation into populations based on cell surface fluorescence intensity derived from the expressed HSA. Significant increases in GC enzyme activity were seen for the transduced and especially the transduced and sorted cells. Similarly, increases in GC specific activity were seen in transduced and sorted skin fibroblasts from a patient with Gaucher disease. To streamline future transfer and sorting protocols for hematopoietic cells, transformed B-cell lines from Gaucher patients were created. Type I B cells were transduced and sorted, and large increases in GC specific activity occurred with concomitant increases in integrated retroviral copy numbers. In addition, toward the goal of using this selectable approach for corrective gene transfer to bone marrow stem cells, CD34+ cells were isolated from normal BM donors, transduced, and sorted based on cell surface expression of HSA. Proviral DNA was detected in approximately 40% of clonogenic progenitor colonies derived from unsorted, transduced CD34+ cells, demonstrating the high titer of the vector. However, after sorting, 100% of the colonies had the corrective GC cDNA, demonstrating the efficiency of this selective system for human hematopoietic progenitors. It is expected that strategies based on this approach will allow sorting of transduced cells of many types before implantation of transduced cells to animals or patients. This vector system may also be used to simplify manipulations and studies on retroviral-mediated gene delivery in vitro and for in vivo models.
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PMID:A bicistronic therapeutic retroviral vector enables sorting of transduced CD34+ cells and corrects the enzyme deficiency in cells from Gaucher patients. 863 21